ABSTRACT The 2011 HHS report on multiple chronic conditions highlighted the prevalence, morbidity, and cost associated with clusters of co-occurring chronic conditions, both physical and mental. Collaborative chronic care models (CCMs) are effective in treating chronic medical and mental illnesses at little to no net healthcare cost. To date CCMs have primarily been implemented at the facility level and adopted by larger, public healthcare organizations. However, the vast majority of primary care and behavioral health practices providing commercially insured care are far too small to implement such models. Health plan-level CCMs can address this unmet need. Based on a groundbreaking partnership with Aetna Inc., the goal of this study is to implement a cross-diagnosis CCM designed to improve outcomes for persons with mood disorders with an eye towards developing a business case for a generalizable plan-level CCM for solo or small practices. Mood disorders (depression and bipolar disorder) were identified by Aetna as priority conditions because of their chronic nature and high healthcare costs. While evidence-based care parameters have been well established, quality of medical and psychiatric care and health outcomes are suboptimal for persons with mood disorders. We will conduct a randomized controlled trial of the cross-diagnosis CCM vs. education control among Aetna beneficiaries across the country who were hospitalized for unipolar depression or bipolar disorder and treated in solo or small primary care or behavioral health practices. At hospitalization discharge a total of 172 solo or small practices involving a total of 344 patients will be randomized to one year of outpatient treatment augmented by the CCM or education control. CCM components include care management that will be fully remote from practice venues and patients, implemented by the Aetna care management center in Salt Lake City, provider guideline support, and web-based self-management support (Life Goals program). The primary health outcomes are mood disorder symptoms, health-related quality of life, hospitalizations, and guideline- based mood disorders and cardiometabolic management. Secondary outcomes include determining the provider and organizational factors associated with CCM outcomes and uptake including health IT capacity, cost effectiveness of the CCM compared to education control, and development of a business plan based on empirical data and stakeholder input. This proposed R18 addresses AHRQ's research demonstration and dissemination priorities, particularly around prevention and care management. In addition to this groundbreaking practice-research partnership focused on solo or small practices to further implement CCMs at the health plan level, this study may also lead to the evolution of the business case for cross-diagnosis CCMs in general, and the utility of plan-level panel management and remote e-health technologies, especially with the advent of accountable care organizations and similar initiatives.